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Objective: To apply the new nomenclature for steatotic liver diseases (SLD), replacing nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD), in adolescents using National Health and Nutrition Examination Survey (NHANES) data., Methods: Among 1410 adolescents (12-19 years) in NHANES (2017-March, 2020), the controlled attenuation parameter (CAP) of transient elastography (TE) was used to define steatosis and fibrosis (TE ≥ 7.4 kPa). Obesity and alanine aminotransferase (ALT) ≥ 80 U/L were used to identify adolescents qualifying for hepatology referral according to practice guidelines. NAFLD was defined as liver steatosis without a specific exposure; it has no cardiometabolic risk factor requirement, unlike MASLD., Results: Steatosis (yes/no) is the first decision point in the new diagnostic protocol; however, criteria for steatosis are undefined. At the supplier (EchoSens)-recommended CAP threshold of 240 dB/m, 30.5% (95% confidence interval [CI]: 27.1%-34.0%) of adolescents had SLD and about 85% of adolescents with NAFLD met criteria for MASLD. The other 15% would receive an ambiguous diagnosis of either cryptogenic SLD or possible MASLD. At higher CAP thresholds, MASLD/NAFLD concordance increased and approached 100%. Among adolescents with MASLD-fibrosis, only 8.8% (95% CI: 0%-19.3%) had overweight/obese and ALT ≥ 80 U/L., Conclusions: The new nomenclature highlights the high prevalence of liver steatosis. At the CAP threshold of 240 dB/m, however, approximately 15% of adolescents would receive an ambiguous diagnosis, which could lead to confusion and worry. Fewer than 10% of adolescents with MASLD-fibrosis had overweight/obese and ALT ≥ 80 U/L. Revised guidelines are needed to ensure that the other 90% receive appropriate referral and liver disease care., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Nonalcoholic fatty liver disease (NAFLD) has been a commonly used term and diagnosis in paediatric hepatology, gastroenterology, and endocrinology clinics for over 30 years. A multisociety Delphi process has determined a new name "Steatotic Liver Disease" (SLD) as the overarching term for disorders associated with hepatic lipid accumulation. Our Societies give our support to steatotic liver disease as the best overarching term for use in our communities. Metabolic dysfunction-associated steatotic liver disease (MASLD) overcomes many of the shortcomings of the name NAFLD. Here, we highlight several points of the new nomenclature that are of particular importance for our community and their consequences for implementation including: diagnostic criteria, considering alternate diagnoses, practical implementation, research, advocacy, and education for paediatricians. As with all nomenclature changes, it will take a concerted effort from our paediatric societies to help integrate the optimal use of this into practice., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Elevated liver enzymes are a primary reason to refer patients for further testing. However, liver enzymes within the normal range do not exclude the presence of MASLD. We examined the prevalence of MASLD in a middle-aged population with overweight and normal liver enzymes. In addition, we examined the accuracy of 4 sets of noninvasive proxies for MASLD. We included 1017 participants from the Netherlands epidemiology of obesity cohort study with body mass index ≥25 kg/m2 and liver enzymes (asparate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidase) within normal range. The diagnostic accuracy of biomarker scores (fatty liver index, liver fat score [LFS], STEATO-ELSA, and hepatic steatosis index) was determined against elevated hepatic triglyceride content measured by 1proton magnetic resonance spectroscopy. Participants (mean age 56 years, 49% women), had a median body mass index of 29.6 kg/m2 and a median hepatic triglyceride content of 4.4%. MASLD was present in 42% of participants and was more common in men than women, with respectively 47% and 36% being affected. The LFS showed the highest accuracy with an area under the curve of 0.72. We identified metabolic syndrome as the prime predictor for MASLD with an odds ratio of 2.95 (95% confidence interval 2.20-3.98). The prevalence of MASLD in middle-aged men and women with overweight and liver enzymes within the normal range is over 40%. LFS showed the highest accuracy to detect MASLD, but, overall, biomarker scores performed relatively poor. The presence of metabolic syndrome was the prime predictor of MASLD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Acute fatty liver of pregnancy (AFLP) is a rare and potentially fatal complication that occurs in the third trimester or early postpartum period. The diagnosis of AFLP is based on typical clinical and laboratory features and imaging examinations., Patient Concerns: Case 1: a 25-year-old pregnant woman was hospitalized for threatened preterm birth at gestation of 35weeks and 2 days gestation. Laboratory tests revealed liver dysfunction, coagulopathy, hypoglycemia, hypoproteinemia, leukocytosis, and elevated creatinine and uric acid levels. Case 2: a 28-year-old (nulliparous) became pregnant after in vitro fertilization-embryo transfer at 29 weeks and 1 days' gestation and came to the obstetric ward for vaginal bleeding. At 34 weeks and 1 day, laboratory investigations showed high serum creatinine, uric acid, liver dysfunction, coagulopathy, and hypoglycemia., Diagnoses: Two patients did not show obvious clinical symptoms, while the ultrasound findings confirmed a diagnosis of AFLP., Interventions: Immediate delivery and comprehensive supportive treatment are the most important methods for the treatment of AFLP., Outcomes: The 2 patients and their babies were discharged from the hospital in a good condition., Lessons: Special attention should be paid to mothers with AFLP after in vitro fertilization-embryo transfer. The clinical presentation of AFLP is variable, hence laboratory features and ultrasound examination may be important methods for screening for AFLP., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Deceased donor and recipient predictors of posttransplant steatosis/steatohepatitis and fibrosis are not well known. Our aim was to evaluate the prevalence and assess donor and recipient predictors of steatosis, steatohepatitis, and fibrosis in liver transplantation recipients., Methods: Using the immune tolerance network A-WISH multicenter study (NCT00135694), donor and recipient demographic and clinical features were collected. Liver biopsies were taken from the donor liver at transplant, and from recipients per protocol and for-cause (ie, abnormal transaminases and to rule out rejection) and were interpreted by a central pathologist., Results: One hundred eighty-three paired donor/recipients liver biopsies at the time of transplant and posttransplant follow-up (median time 582 d; average time to last biopsies was 704 d [SD ± 402 d]) were analyzed. Donor steatosis did not influence recipient steatosis or fibrosis. Ten of 183 recipients had steatohepatitis on the last biopsy. Recipient body mass index at the time of liver biopsy was the most influential factor associated with posttransplant steatosis. Both donor and recipient metabolic syndrome features were not associated with graft steatosis. Untreated hepatitis C viral (HCV) infection was the most influential factor associated with the development of allograft fibrosis., Conclusions: In a large experience evaluating paired donor and recipient characteristics, recipient body mass index at the time of liver biopsy was most significantly associated with posttransplant steatosis. Untreated HCV etiology influenced graft fibrosis. Thus relative to untreated HCV, hepatic fibrosis in those with steatosis/steatohepatitis is less common though long-term follow-up is needed to determine the course of posttransplant fibrosis. Emphasis on recipient weight control is essential., Competing Interests: K.R.R. received advisory board from Abbvie, Gilead, Merck, BMS, Spark Therapeutics, Dova, Shionogi, and Mallinckrodt and research grants (paid to the University of Pennsylvania) from Merck, Gilead, Mallinckrodt, BMS, Abbvie, Grifols, Intercept, Conatus, and Exact Sciences. None of these conflict with the current work. S.F. received consulting from BioMarin Pharmaceutical and Research from Novartis. None of these conflict with the current work. The other authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Wilson disease (WD) is a copper metabolism disorder with toxic copper accumulation in the liver leading to liver steatosis or fibrosis. In vitro studies suggest that fatty acid-binding protein 1 (L-FABP) and lipid droplet-associated protein 5 (PLIN5) may have an impact on both processes, but knowledge about these potential biomarkers is insufficient in the case of WD. Thus, the aim of this study was to determine L-FABP and PLIN5 levels in sera of WD patients in relation to liver steatosis/fibrosis., Methods: The final study involved 74 WD children in whom liver steatosis (WD1 subgroup, n = 28) and fibrosis (WD2 subgroup, n = 13) were assessed with the use of transient elastography. Control groups included WD children without steatosis and fibrosis (WD0 subgroup, n = 33) and healthy children (n = 75). L-FABP and PLIN5 measurements were performed in sera with the use of the immunoenzymatic method., Results: L-FABP was significantly higher in the WD2 subgroup, and the correlation between L-FABP concentration and liver fibrosis was confirmed statistically by regression analysis (P = 0.04) with Pearson's coefficient r = 0.24. L-FABP was significantly correlated with alanine aminotransferase (r = 0.42) and aspartate aminotransferase (r = 0.37) activity. PLIN5 concentration was similar in all groups and was not related to steatosis and fibrosis., Conclusions: Our results suggest that serum L-FABP could be a novel biomarker of liver fibrosis in WD children., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest.

Rationale: Transient infantile hypertriglyceridemia (HTGTI) is a rare autosomal recessive inherited disease caused by inactivating mutations in the glycerol-3-phosphate dehydrogenase 1 gene. To date, only a few patients have been reported worldwide. The symptoms of the affected individuals present a certain degree of transient hypertriglyceridemia, hepatomegaly, elevated liver enzymes, persistent fatty liver and hepatic fibrosis in early infancy. However, the clinical characteristics and pathogenesis of this disease are remain unclear., Patient Concerns: A one month and twenty-five days old girl was admitted to hospital because of persisted jaundice and hepatomegaly for fifty days., Diagnose: The girl was diagnosed with HTGTI coincident with a noval mutation in glycerol-3-phosphate dehydrogenase 1., Intervention: She was advised to take low-fat diet and supplement of medium-chain fatty acids., Outcomes: Her jaundice was gradually normal at the age of 4 months without any treatment, and hypertriglyceridemia were normal at the age of 13 months, but still had elevated transaminases and hepatic steatosis., Lessons: Jaundice may be a novel phenotype in HTGTI. The report contributes to the expansion of HTGTI's gene mutation spectrum and its clinical manifestations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Acutefatty liver of pregnancy (AFLP) is a potentially fatal obstetric emergency characterized by acute hepatic failure secondary to fatty infiltration. The resultant effects include coagulopathy, electrolyte abnormalities, and multisystem organ dysfunction. Pancreatitis typically develops after the onset of renal and hepatic dysfunction. Pancreatitis has been suggested as a poor prognostic indicator because it is associated with more adverse outcomes., Patient Concerns: A 29-year-old Chinese woman at 34.7 weeks pregnancy was admitted to hospital due to paroxysmal hypogastric pain and massive colporrhagia for 1 day., Diagnosis: Laboratory tests revealed hepatic and renal impairment, coagulopathy. Thoracoabdominal computed tomography (CT) scanning showed pleural and peritoneal effusion, fatty liver, and pancreatitis. She was diagnosed with AFLP, severe acute pancreatitis (SAP), multiple organ dysfunction syndrome (MODS), and intrauterine fetal death., Interventions: The patient was treated with blood component transfusions, plasma exchange combined with renal replacement therapy, antibiotic de-escalation, gastric and pancreatic secretion inhibitor, and enteral nutrition., Outcomes: After successful management, the patient was discharged without any complications on day 35 of admission. At 10 months follow-up, thoracoabdominal enhanced CT revealed was normal and laboratory tests revealed normal liver and kidney function., Lessons: Once AFLP is highly suspected or confirmed, the pregnancy should be terminated in time and active symptomatic management should be given., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Acute fatty liver of pregnancy is a rare, but potentially fatal obstetric disorder characterized principally by varying degrees of hepatic failure with an onset typically in late pregnancy. This review outlines the etiopathogenesis and describes the multiorgan involvement that often results in a number of clinical and laboratory aberrations. These laboratory derangements provide distinct features to differentiate from other obstetric complications, such as hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Once recognized, central to the management of acute fatty liver of pregnancy is delivery planning and meticulous supportive care. One particularly dangerous complication is profound coagulopathy. After delivery, the coagulation defect resolves over 1-2 days, and hepatic and renal function are restored soon thereafter. This report offers anticipated recovery and management strategies for commonly associated complications. Application of these factors has served to decrease mortality from as high as 80% down to 10%; however, given the seriousness of this condition, severe maternal morbidities are frequently associated with this obstetric emergency., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The prevalence and impact of hepatic steatosis among patients with autoimmune hepatitis (AIH) is not well described.We conducted a cross-sectional study to determine the prevalence of hepatic steatosis in AIH patients and examined its relationship with hepatic fibrosis using vibration controlled transient elastography. Liver stiffness measurement (LSM), controlled attenuation parameter (CAP), gender, current age, and body mass index (BMI) were collected from 277 AIH patients. Hepatic steatosis was defined as CAP >263 db/m.The study participants were mostly female (82%) with an average age of 49 years and BMI 29.7 kg/m. Mean LSM was 12.5 (standard deviation 13.5) kPa and CAP was 244 (standard deviation 63) db/m. The prevalence of coexisting steatosis was 33.2%, and steatosis did not correlate with LSM (r = 0.05, P = .46). In this study, only gender (females with 31% lower LSM on average compared to males, P = .001) and BMI (each unit increase of BMI resulted in a 1.48% increase on average LSM, P = .01) correlated with LSM. Male gender had significant association with increased LSM, after controlling for age, BMI, and CAP (P = .001).This exploratory study using noninvasive vibration controlled transient elastography revealed hepatic steatosis is highly prevalent in patients with AIH but not associated with liver fibrosis.

Background: Donor livers with ≥30% macrosteatosis (steatotic livers) represent a possible expansion to the donor pool, but are frequently discarded as they are associated with an increased risk of mortality and graft loss. We hypothesized that there are certain recipient phenotypes that would tolerate donor steatosis well, and are therefore best suited to receive these grafts., Methods: Using national registry data from the Scientific Registry of Transplant Recipients between 2006 and 2017, we compared 2048 liver transplant recipients of steatotic livers with 69 394 recipients of nonsteatotic (<30%) livers. We identified recipient factors that amplified the impact of donor steatosis on mortality and graft loss using interaction analysis, classifying recipients without these factors as preferred recipients. We compared mortality and graft loss with steatotic versus nonsteatotic livers in preferred and nonpreferred recipients using Cox regression., Results: Preferred recipients of steatotic livers were determined to be first-time recipients with a model for end-stage liver disease 15-34, without primary biliary cirrhosis, and not on life support before transplant. Preferred recipients had no increased mortality risk (hazard ratio [HR]: 0.921.041.16; P = 0.5) or graft loss (HR: 0.931.031.15; P = 0.5) with steatotic versus nonsteatotic livers. Conversely, nonpreferred recipients had a 41% increased mortality risk (HR: 1.171.411.70; P < 0.001) and 39% increased risk of graft loss (HR: 1.161.391.66; P < 0.001) with steatotic versus nonsteatotic livers., Conclusions: The risks of liver transplantation with steatotic donor livers could be minimized by appropriate recipient matching.

Background: Steatotic donor livers (SDLs, ≥30% macrosteatosis on biopsy) are often declined, as they are associated with a higher risk of graft loss, even though candidates may wait an indefinite time for a subsequent organ offer. We sought to quantify outcomes for transplant candidates who declined or accepted an SDL offer., Methods: We used Scientific Registry of Transplant Recipients offer data from 2009 to 2015 to compare outcomes of 759 candidates who accepted an SDL to 13 362 matched controls who declined and followed candidates from the date of decision (decline or accept) until death or end of study period. We used a competing risk framework to understand the natural history of candidates who declined and Cox regression to compare postdecision survival after declining versus accepting (ie, what could have happened if candidates who declined had instead accepted)., Results: Among those who declined an SDL, only 53.1% of candidates were subsequently transplanted, 23.8% died, and 19.4% were removed from the waitlist. Candidates who accepted had a brief perioperative risk period within the first month posttransplant (adjusted hazard ratio [aHR]: 2.493.494.89, P < 0.001), but a 62% lower mortality risk (aHR: 0.310.380.46, P < 0.001) beyond this. Although the long-term survival benefit of acceptance did not vary by candidate model for end-stage liver disease (MELD), the short-term risk period did. MELD 6-21 candidates who accepted an SDL had a 7.88-fold higher mortality risk (aHR: 4.807.8812.93, P < 0.001) in the first month posttransplant, whereas MELD 35-40 candidates had a 68% lower mortality risk (aHR: 0.110.320.90, P = 0.03)., Conclusions: Appropriately selected SDLs can decrease wait time and provide substantial long-term survival benefit for liver transplant candidates.

Rationale: Acute fatty liver of pregnancy (AFLP) is extremely hazardous to pregnant woman in the 3rd trimester of pregnancy. AFLP has an insidious onset and nonspecific experimental indicators, which therefore is difficult to be diagnosed., Patient Concerns: Case 1 was transferred to our hospital for hypertensive disorders complicating pregnancy at gestation of 38 weeks + 3 days. Case 2 was transferred to our hospital for suspicious fetal heart monitoring response at gestation of 36 weeks + 4 days. Case 3 was transferred to our hospital for prelabor rupture of membranes at gestation of 37 weeks + 1 days., Diagnosis: The diagnosis of AFLP was based on the Swansea criteria., Interventions: All 3 cases were delivered by cesarean section, and they were all transferred to intensive care unit for further treatment. Cases 2 and 3 were subjected to plasma exchange and continuous renal replacement therapy., Outcomes: In this study, all 3 patients were initially diagnosed as gastritis. In addition, case 1 was diagnosed as preeclampsia and her AFLP was misdiagnosed with postpartum hemorrhage after cesarean delivery. Case 2 was admitted to the hospital for intrahepatic cholestasis of pregnancy and fetal distress, but we considered it as AFLP before delivery. Case 3 was treated according to severe intrahepatic cholestasis of pregnancy, but we rediagnosed it as postpartum hemorrhage and disseminated intravascular coagulation after cesarean delivery. Neonatal asphyxia and complications were not found. All of the 3 cases were fully recovered and discharged from our hospital., Lessons: If there are multiple risk factors including vomiting, abdominal pain, and fetal distress, AFLP should be highly suspected. Early diagnosis, especially before termination of pregnancy, is the key to successful treatment of AFLP.

Background: Our aim was to evaluate liver transplant outcomes involving donors with high macrosteatosis grafts in the obese modern liver transplant recipient population., Methods: A high-steatosis graft was defined as donor graft macrosteatosis ≥30% on biopsy. Recipient obesity was defined as body mass index (BMI) >35 adjusted for ascites. Raw and adjusted recipient liver transplant survival were evaluated and compared between 4 cohorts: (1) high-steatosis graft in high-BMI recipient; (2) low-steatosis graft in high-BMI recipient; (3) high-steatosis graft in normal-BMI recipient; and (4) low-steatosis graft in normal-BMI recipient., Results: After adjustment for multiple factors, recipient high-BMI remained an independent predictor of posttransplant mortality at 30 days (P < 0.0001) and persisted at 1 year (P = 0.009). A high-steatosis graft was the strongest independent predictor of mortality at 30 days (hazard ratio 2.05, 1.66-2.53; P < 0.0001) and that effect was diminished but persistent at 1 year (1.27, 1.10-1.46; P = 0.001)., Conclusions: Recipient high-BMI and a high-steatosis graft are both significant independent and equally powerful predictors of mortality after modern liver transplant. High-steatosis grafts transplanted into obese recipients have the highest mortality. The increase in mortality associated with a high-steatosis graft into a normal-BMI recipient is similar in magnitude to a low-steatosis graft placed into a high-BMI recipient.

Acute fatty liver of pregnancy (AFLP) is a rare, but potentially fatal condition, characterized by hepatic failure typically in the third trimester of pregnancy that is associated with multiorgan involvement resulting in a number of clinical and laboratory abnormalities. The cornerstone of management of AFLP includes prompt recognition, preparation for delivery, and supportive care such as reversal of coagulopathy. Early diagnosis, prompted delivery, and supportive care have resulted in improved maternal morbidity and mortality. This review focuses on the epidemiology, etiology, clinical presentation, diagnosis, management, and resolution of AFLP.

Background: The true incidence and unique risk factors for recurrent and de novo nonalcoholic fatty liver (NAFLD) and nonalcoholic steatohepatitis (NASH) post-liver transplant (LT) remain poorly characterized. We aimed to identify the incidence and risk factors for recurrent and de novo NAFLD/NASH post-LT., Methods: MEDLINE via PubMed, Embase, Scopus, and CINAHL were searched for studies from 2000 to 2018. Risk of bias was adjudicated using the Newcastle-Ottawa Scale., Results: Seventeen studies representing 2378 patients were included. All were retrospective analyses of patients with post-LT liver biopsies, with the exception of 2 studies that used imaging for outcome assessment. Seven studies evaluated occurrence of recurrent NAFLD/NASH, 3 evaluated de novo occurrence, and 7 evaluated both recurrent and de novo. In studies at generally high or moderate risk of bias, mean 1-, 3-, and ≥5-year incidence rates may be 59%, 57%, and 82% for recurrent NAFLD; 67%, 40%, and 78% for de novo NAFLD; 53%, 57.4%, and 38% for recurrent NASH; and 13%, 16%, and 17% for de novo NASH. Multivariate analysis demonstrated that post-LT body mass index (summarized odds ratio = 1.27) and hyperlipidemia were the most consistent predictors of outcomes., Conclusions: There is low confidence in the incidence of recurrent and de novo NAFLD and NASH after LT due to study heterogeneity. Recurrent and de novo NAFLD may occur in over half of recipients as soon as 1 year after LT. NASH recurs in most patients after LT, whereas de novo NASH occurs rarely. NAFLD/NASH after LT is associated with metabolic risk factors.

We investigated associations between inflammatory marker levels and hepatitis C virus (HCV)-related compensated liver cirrhosis risk in patients with chronic hepatitis C (CHC) infection in China. We used a case-control design and data from the records of 110 Chinese patients with CHC and cirrhosis for the study; 458 CHC patients who did not have a diagnosis of cirrhosis were matched to the case group by age and sex characteristics. We also investigated fatty liver disease risk factors. The group of patients with CHC infection and cirrhosis had lower platelet-to-lymphocyte ratio (PLR) values (60.63 [44.09, 89.31]) compared with the control group patients (80.24 [57.85, 111.08]). The results indicated that the group of patients with cirrhosis had higher 4-factor fibrosis index and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) values compared with the group of patients with CHC-only (1.66 [0.98, 2.60] vs 0.71 [0.45, 1.17], respectively; P < .001 and 2.12 [0.97, 4.25] vs 0.99 [0.51, 2.01], respectively; P < .001). Compared with the control group, the AST/alanine aminotransferase ratio (AAR) values in the group of patients with cirrhosis were significantly higher (P < .001). Logistic regression analysis that included model adjustment for demographic characteristics and other factors that could affect cirrhosis risk revealed that greater 1/PLR values were associated with an increased odds of having cirrhosis (adjusted odds ratio [AOR], 95% confidence interval [CI] 0.991 [0.985-0.996]); APRI and AAR values were also independent predictors of the presence of compensated cirrhosis. We found that compared with the patients with CHC-only, the triglyceride, cholesterol, and low-density lipoprotein cholesterol levels in the patients with both CHC and fatty liver disease were significantly higher. The multivariate analysis of the risk of fatty liver development in patients with CHC infection found that cholesterol level was a statistically significant risk factor (AOR [95% CI] 1.380 [1.089-1.750], P = .008). Increased 1/PLR, APRI, and AAR values were associated with increased risks for development of cirrhosis in this population of Chinese patients with CHC infection. Higher cholesterol levels increased the risk of development of fatty liver disease in patients with CHC.

Nonalcoholic fatty liver disease is a growing condition among adolescent and adult populations, present in around 20%-30% of people in the United Kingdom. Nonalcoholic fatty liver disease is known as a silent disease and over many years may go on to cause nonalcoholic steatohepatitis. In the future it may become a leading contributor to cirrhosis, liver transplantation, and mortality. In recent years, programs have been set up to raise awareness of this condition with the first International NASH (nonalcoholic steatohepatitis) Day taking place in 2018; nevertheless, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis is still not clearly understood by many. An extensive review has shown a lack of nursing literature on this topic, and effective specialist nurse input for this patient group should be a key component in tackling this growing epidemic in the years to come.

Because of the shortage of liver grafts available for transplantation, the restrictions on graft quality have been relaxed, and marginal grafts, such as steatotic livers, are now accepted. However, this policy change has not solved the problem, because steatotic liver grafts tolerate ischemia-reperfusion (I/R) injury poorly. Adipocytokines differentially modulate steatosis, inflammation, and fibrosis and are broadly present in hepatic resections and transplants. The potential use of adipocytokines as biomarkers of the severity of steatosis and liver damage to aid the identification of high-risk steatotic liver donors and to evaluate hepatic injury in the postoperative period are discussed. The hope of finding new therapeutic strategies aimed specifically at protecting steatotic livers undergoing surgery is a strong impetus for identifying the mechanisms responsible for hepatic failure after major surgical intervention. Hence, the most recently described roles of adipocytokines in steatotic livers subject to I/R injury are discussed, the conflicting results in the literature are summarized, and reasons are offered as to why strategic pharmacologic control of adipocytokines has yet to yield clinical benefits. After this, the next steps needed to transfer basic knowledge about adipocytokines into clinical practice to protect marginal livers subject to I/R injury are presented. Recent strategies based on adipocytokine regulation, which have shown efficacy in various pathologies, and hold promise for hepatic resection and transplantation are also outlined.

Background: Posttransplant liver steatosis occurs frequently and can affect patient outcome. Our aim was to clarify the risk factors for steatosis or steatohepatitis after living donor liver transplantation (LT) through a retrospective examination of recent 100 living donor LT recipients and their liver donors., Methods: Liver biopsy was performed at 1 year after LT and each year, thereafter, or as needed due to abnormal liver enzyme levels, with a median follow-up of 4 years (2-10 years)., Results: Liver steatosis (≥5%) was identified in 33 cases, with steatohepatitis identified in 9 of 33 patients with liver steatosis. Recipients with liver steatosis were younger than those without steatosis (53.4 ± 9.5 years vs 57.6 ± 9.9 years, respectively; P = 0.045). Of note, the prevalence of steatosis was significantly higher among LT recipients who received a graft from a donor with steatosis than without (60% vs 23%, respectively; P = 0.001). Donor steatosis was also associated with steatohepatitis in recipients after LT (steatohepatitis/simple steatosis, 88%:50%). On multivariate analysis, younger recipient age (P = 0.023) and donor steatosis (P = 0.005) were independent risk factors of liver steatosis after LT. Among the 33 recipients in our study group, 26 were assessed by serial liver biopsies, with 6 showing progression of the nonalcoholic fatty liver disease activity score. An increase in body weight was predictive of steatosis progression after LT (P = 0.005)., Conclusions: Age and donor steatosis influence the risk of liver steatosis and steatohepatitis in recipients after LT. The clinical course of steatosis is relatively benign, with only 19% developing nonalcoholic fatty liver disease activity score and 7.6% significant fibrosis.

Purpose of Review: Polycystic ovary syndrome (PCOS) is defined by hyperandrogenism, irregular menses and polycystic ovaries when other causes are excluded. The possible implication of increased morbidity in PCOS for screening and follow-up is uncertain and is reviewed in this article., Recent Findings: The increased risk of type 2 diabetes and cardiovascular disease in PCOS is closely associated with BMI. Women with PCOS should be screened for the elements of the metabolic syndrome upon diagnosis. Measurement of HbA1c and the lipid accumulation product could be important tools to differentiate women with high metabolic risk. The immune function in PCOS is impaired with increased secretion of autoantibodies and increased risk of type 1 diabetes, asthma and thyroid disease. The occurrence of thyroid disease could be modified by BMI and D-vitamin status. Screening for diabetes and thyroid disease is part of routine evaluation for endocrine diseases at baseline in PCOS, whereas the necessity of prospective screening for thyroid disease awaits future studies. Especially obese women with PCOS are at an increased risk of nonalcoholic fatty liver disease, gall bladder disease and endometrial cancer., Summary: Recent data support that screening and follow-up in patients with PCOS should be stratified according to BMI.

The recently developed magnetic resonance imaging (MRI) proton density fat fraction (PDFF) allows measurement of the fat in all segments of hepatic tissue. However, it is time consuming and inconvenient to measure each segment repeatedly. Moreover, volume of each segment also should be adjusted with arithmetic mean of the selected segments when total amount of liver fat is estimated. Therefore, we try to develop a clinically-relevant and applicable method of estimating hepatic fat in PDFF image.A total of 164 adults were enrolled. We addressed the measurement frequency and segment selection to determine the optimal method of measuring intrahepatic fat. Total hepatic fat was estimated by the weighted mean of each segment reflecting their respective segmental volumes. We designed 2 models. In Model 1, we determined the segment order by which the mean was closest to the whole weighted mean. In Model 2, we determined the segment order by which the arithmetic mean of the selected segments was closest to the whole weighted mean.Fat fraction (FF) was most important risk factor of hepatic heterogeneity in multivariable analysis (β = 0.534, P < .001). In severe fatty liver (FF > 22.1%), intrahepatic fat variability was 2.47% (1.16-6.26%). The arithmetic mean total intrahepatic FF was 12.66%. But the weighted mean that applied to each segmental volume was 12.90%. In Model 1, arithmetic mean of segments 4 and 5 was closest to the total estimated hepatic fat amount. However, when we added segment 8, the mean of segments 4, 5, and 8 was significantly different from the estimated total hepatic fat amount (P = .0021). In Model 2, arithmetic mean of segments 4 and 5 was closest to the total estimated hepatic fat amount. There was a significant reduction in variability between segment 4 and segments 4 and 5 (P < .0001).Averaging the mean hepatic FF of segments 4 and 5 was the most reasonable method for estimating total intrahepatic fat in practice.

Purpose of Review: Nonalcoholic fatty liver disease (NAFLD) is common among patients living with HIV and may lead to liver-related morbidity and mortality., Recent Findings: The prevalence of NAFLD among patients with HIV is increasingly well described due to new noninvasive techniques to quantify hepatic steatosis and fibrosis. Patients with HIV may be at increased risk of disease progression, though high-quality natural history studies are not available. The high rates of metabolic syndrome, dyslipidemia and insulin resistance may partially account for this excess risk, though the impact of HIV itself, antiretroviral medications and dysregulation of the gut-liver axis likely play important roles. Treatment of NAFLD in patients with HIV is poorly studied. Current recommendations include diet and lifestyle modifications, HIV viral suppression and limitation of hepatotoxic medications as possible. In addition, there are a large number of novel medications now in clinical trials designed to target the accumulation of hepatic fat, oxidative stress, inflammation and/or fibrosis, which will revolutionize this field., Summary: Although additional work is needed to understand the natural history of NAFLD in patients with HIV and identify those at highest risk, novel treatment approaches are now being tested in this population. We may soon have effective treatments to combat this epidemic.

Nonalcoholic fatty liver disease has been suggested to be associated with alanine aminotransferase (ALT) elevation in hepatitis B virus (HBV)-infected patients with HBe antigen (HBeAg)-negativity and a low HBV-DNA level. However, few studies have evaluated the association according to histological findings of the liver.Among a total of 198 HBV-infected patients who received a percutaneous liver biopsy, we studied the histological and laboratory findings of HBeAg-negative patients without receiving nucleoside/nucleotide analogues treatment (N = 70) in order to evaluate whether hepatic steatosis and its related metabolic disorders were associated with an elevation in ALT levels in HBeAg-negative patients.In HBeAg-negative patients with a high serum HBV-DNA level (≥2000 IU/mL), the level of HBV-DNA was the only significant factor related to ALT elevation. However, in HBeAg-negative patients with a low HBV-DNA level, the serum ferritin level, and histologically observed hepatic steatosis were significantly associated factors with ALT elevation. When we evaluated 2 metabolic variables (serum ferritin and fasting insulin) that are suggested to be relevant to the presence of progressive disease in Japanese patients, we found that the rate of metabolic disorders was significantly higher among patients with a high ALT level and a low HBV-DNA level than it was among those with other conditions. The triglyceride level and the frequency of moderate or severe hepatic steatosis were significantly higher in patients with a low HBV-DNA level than in those with a high HBV-DNA level.Histologically proven hepatic steatosis and its related metabolic disorders are suggested to be involved in the elevation of aminotransferases of HBeAg-negative patients, particularly those with low HBV-DNA levels., Competing Interests: The authors have no conflicts of interest to disclose.

Hepatic steatosis assessment is of paramount importance for living liver donor selection because significant hepatic steatosis can affect the postoperative outcome of recipients and the safety of the donor. The validity of various noninvasive imaging methods to assess hepatic steatosis remains controversial. The purpose of our study is to investigate the association between noninvasive imaging methods and pathology to detect steatosis in living liver donors and to propose a prediction model for hepatic steatosis. Liver stiffness measurements (LSMs) and controlled attenuation parameter values in vibration controlled transient elastography, ultrasonography, computed tomography (CT), and magnetic resonance imaging were used as pretransplant screening methods to evaluate living liver donors between 2012 and 2014. Only 1 pathologist assessed tissue sample for hepatic steatosis. The median age of the 79 living donors (53 men and 26 women) was 32 years (16-68 years). The CT liver-spleen attenuation (L-S) difference and the controlled attenuation parameter values were well correlated with the level of hepatic steatosis on liver pathology. Multivariate analysis showed that liver stiffness measurement (LSM) (β = 0.903; 95% CI, 0.105-1.702; P = 0.027) and the CT L to S attenuation difference (β = -3.322; 95% CI, -0.502 to -0.142; P = 0.001) were closely associated with hepatic steatosis. We generated the following equation to predict total hepatic steatosis: Hepatic steatosis = 0.903 × LSM - 0.322 × CT L to S attenuation difference (AUC = 86.6% and P = 0.001). The values predicted by the equation correlated well with the presence of hepatic steatosis (r = 0.509 and P < 0.001). The combination of nonenhanced CT L to S attenuation difference and transient elastography using vibration controlled transient elastography provides sufficient information to predict hepatic steatosis in living liver donor candidates., Competing Interests: The authors have no conflicts of interest to disclose.

Considering limitations of liver biopsy for diagnosis of nonalcoholic liver disease (NAFLD), biomarkers' panels were proposed. The aims of this study were to establish models based on serum adipokines for discriminating NAFLD from healthy individuals and nonalcoholic steatohepatitis (NASH) from simple steatosis.This case-control study was conducted in patients with persistent elevated serum aminotransferase levels and fatty liver on ultrasound. Individuals with evidence of alcohol consumption, hepatotoxic medication, viral hepatitis, and known liver disease were excluded. Liver biopsy was performed in the remaining patients to distinguish NAFLD/NASH. Histologic findings were interpreted using "nonalcoholic fatty liver activity score." Control group consisted of healthy volunteers with normal physical examination, liver function tests, and liver ultrasound. Binary logistic regression analysis was applied to ascertain the effects of independent variables on the likelihood that participants have NAFLD/NASH.Decreased serum adiponectin and elevated serum visfatin, IL-6, TNF-a were associated with an increased likelihood of exhibiting NAFLD. NAFLD discriminant score was developed as the following: [(-0.298 × adiponectin) + (0.022 × TNF-a) + (1.021 × Log visfatin) + (0.709 × Log IL-6) + 1.154]. In NAFLD discriminant score, 86.4% of original grouped cases were correctly classified. Discriminant score threshold value of (-0.29) yielded a sensitivity and specificity of 91% and 83% respectively, for discriminating NAFLD from healthy controls. Decreased serum adiponectin and elevated serum visfatin, IL-8, TNF-a were correlated with an increased probability of NASH. NASH discriminant score was proposed as the following: [(-0.091 × adiponectin) + (0.044 × TNF-a) + (1.017 × Log visfatin) + (0.028 × Log IL-8) - 1.787] In NASH model, 84% of original cases were correctly classified. Discriminant score threshold value of (-0.22) yielded a sensitivity and specificity of 90% and 66% respectively, for separating NASH from simple steatosis.New discriminant scores were introduced for differentiating NAFLD/NASH patients with a high accuracy. If verified by future studies, application of suggested models for screening of NAFLD/NASH seems reasonable.

Objectives: To evaluate the incidence of hepatic steatosis after pancreatectomy and whether pancrelipase improves steatosis more effectively than other conventional digestive enzymes., Methods: Patients who underwent distal pancreatectomy, pancreaticoduodenectomy (PD), or total pancreatectomy (TP) from August 2008 to July 2013 were included. Incidence of newly developed hepatic steatosis recognized by computed tomography and outcomes by treatment with pancrealipase or other enzymes were evaluated., Results: A total of 473 patients were evaluated. Among 366 patients who did not take any digestive enzymes until the recognition of steatosis or the last follow-up date, hepatic steatosis was recognized in 3% (4/130), 17% (38/229), and 45% (3/7) of patients after distal pancreatectomy, PD, and TP, respectively, during the median follow-up of 641 days. Seventy patients including 25 patients taking digestive enzymes showed hepatic steatosis and were treated with pancrelipase (20 patients), other enzymes (19 patients), or no enzyme (31 patients). Cumulative improvement rate after 1 year of treatment in the 3 groups was 92%, 51%, and 56%, respectively, and that of the pancrelipase group was significantly better than the other 2 groups., Conclusion: The risk of hepatic steatosis should be a concern after PD and TP. Treatment with pancrelipase was more effective compared to other enzymes.

Purpose of Review: The association of dietary intake and fatty liver disease (FLD) is of importance for disease prevention. Dietary pattern analysis enables the investigation of overall diet and permits to take interactions and cumulative effects of dietary components into account. This review summarizes recent findings on the association of dietary patterns and FLD., Recent Findings: A systematic review of articles published from March 2013 to August 2014 identified four relevant observational (n = 116-995) and one interventional study (n = 12). The Healthy Eating Index and Dietary Diversity Scores were not related to nonalcoholic FLD. A Mediterranean diet intervention resulted in a significant decrease in liver fat content over 6 weeks. Exploratory approaches revealed a 'Western pattern' and a pattern having alcohol, meat (poultry) and tea in common with a hypothesis-driven pattern, which were both associated with FLD., Summary: Most studies were limited by a cross-sectional design and small-to-moderate sample sizes. Observational studies applying exploratory approaches and a Mediterranean diet intervention demonstrated most promising results relating dietary patterns to FLD. Prospective studies with measurement of liver fat on a continuous scale at multiple time points in large samples are important requisites to improve our understanding of FLD cause.

Acute fatty liver of pregnancy, although rare, is usually a third trimester of pregnancy occurrence that may be life threatening for both the pregnant woman and the fetus. Often, the onset resembles gastroenteritis or cholecystitis and correct diagnosis is delayed. Because it can also present with preeclampsia and eclampsia, it may be mistakenly diagnosed as hemolysis, elevated liver enzymes, low platelet syndrome. This article presents diagnostic differences between liver conditions that can complicate pregnancy and management strategies for treating and maintaining the well-being of pregnant women, fetuses, and infants who are affected by acute fatty liver of pregnancy. Early recognition and rapid intervention from antepartum diagnosis through delivery and the postpartum period are required by the nursing team and medical providers to reduce maternal and neonatal morbidity and mortality.

Objective: To assess the prevalence and factors associated with significant hepatic steatosis (SHS, steatosis involving ≥10% hepatocytes) in HIV-infected patients., Design: A prospective, cross-sectional study., Methods: Five hundred and five HIV-infected patients were included in this study. All patients underwent a transient elastography examination with the controlled attenuation parameter (CAP). SHS was defined using the previously identified CAP cut-off of 238 dB/m. We analysed the associations between SHS and demographics, metabolic data, coinfections and drug therapy., Results: SHS was detected in 201 (40%) patients. Individuals with and without plasma HIV RNA of 50 copies/ml or less presented SHS in 168 (42%) and 33 (31%) cases, respectively (P = 0.030). Patients with SHS compared with those without SHS presented higher median (IQR) BMI [BMI, 25.6 (22.5-28) vs. 22.3 (20.3-24.2) kg/m; P < 10], DBP [79 (72-85) vs. 74 (68-81) mmHg; P = 0.0001], fasting plasma glucose [95 (87-106) vs. 91 (84-97) mg/dl; P = 0.002] and triglycerides [128 (92-189) vs. 109 (80-167) mg/dl; P = 0.002], and lower HDL cholesterol [44 (37-54) vs. 48 (40-59), mg/dl; P = 0.004]. In multivariate analysis, the only factor associated with SHS was BMI [per unit increase, adjusted odds ratio (95% confidence interval) 1.34 (1.22-1-47); P < 10]., Conclusion: SHS measured by CAP is highly prevalent among HIV-infected patients. High BMI is the main predictor of SHS in this setting.

Preoperative evaluation of donors for living-donor liver transplantation aims to select a suitable donor with optimal graft quality and to ensure donor safety. Hepatic steatosis, a common finding in living liver donors, not only influences the outcome of liver transplantation for the recipient but also affects the recovery of the living donor after partial hepatectomy. Histopathologic analysis is the reference standard to detect and quantify fat in the liver, but it is invasive, and results are vulnerable to sampling error. Imaging can be repeated regularly and allows assessment of the entire liver, thus avoiding sampling error. Selection of appropriate imaging methods demands understanding of their advantages and limitations and the suitable clinical setting. This article describes potential clinical applications for liver fat quantification of imaging methods for fat detection and quantification, with an emphasis on the advantages and limitations of ultrasonography, computed tomography, and magnetic resonance imaging for quantifying liver fat.

Nonalcoholic steatohepatitis (NASH) is increasingly recognized as the most common chronic liver disease worldwide. The aim of this study is to investigate the transplantation trends of liver transplant (LT) recipients with NASH. Using the United Network for Organ Sharing database, we found a steady increase in LT rate especially in those more than 65 years old. We identified differences across ethnic groups and United Network for Organ Sharing regions. This study highlights the impact of the rising prevalence of NASH on the demand for LT and provides invaluable information to healthcare policymakers and the transplant community about the target groups and geographic location for focused and early intervention.

Objective: LIPA gene mutations result in deficiency of lysosomal acid lipase and present phenotypically as Wolman disease or cholesteryl ester storage disease (CESD) depending on the level of deficiency. Patients with CESD may often be misdiagnosed because symptoms may be nonspecific. Symptoms may present in infancy if there is complete loss of lysosomal acid lipase or in early childhood or adulthood when there is partial loss. The purpose of the present study is to review the literature for pediatric cases of CESD to better understand the phenotype of CESD., Methods: A PubMed search of all English-language publications from 1966 through June 2012 for pediatric CESD case reports using the following key words CESD, fatty liver, and NAFLD was performed. All of the cases were reviewed and information regarding age, sex, presenting symptoms, and pertinent laboratory tests were recorded., Results: Seventy-one cases were culled from 39 published case reports. Nearly two-thirds of these patients presented with their first symptoms when they were younger than 5 years. Hepatomegaly and splenomegaly were common features. Serum transaminases and lipids were often elevated. Gastrointestinal symptoms were noted in approximately one-third of cases. Two-thirds of patients had liver fibrosis., Conclusions: CESD has an estimated incidence as high as 1 in 40,000, which means that it is presently underdiagnosed. Education about common symptoms of CESD as well as a higher level of suspicion for screening for CESD will lead to earlier diagnosis. New treatments for CESD including possible enzyme replacement therapy make early diagnosis especially important.

Purpose of Review: Nonalcoholic fatty liver disease (NAFLD) is a multicluster disease ranging from intrahepatic simple steatosis to nonalcoholic steatohepatitis (NASH). During the last decade, NAFLD has reached epidemic proportions in overweight/obese children. In this manuscript, we review all recent advances in paediatric NAFLD., Recent Findings: Paediatric NAFLD displays some common aspects with the adult form of disease. However, recent findings have demonstrated that regarding development of NAFLD in children, due to the absence of long-time confounding factors, it may be more appropriate to investigate genetic and pathogenetic origins of the disease. Furthermore, as the histological pattern of paediatric NAFLD is different from those observed in adults, specific diagnostic/management programmes and diagnostic scores have been recently developed. Accordingly, several studies demonstrated that both lifestyle intervention and pharmacological treatments should be adequate to the specific pattern of NAFLD in children., Summary: Results of this year's investigations further elucidated the histological features and genetic background that characterize paediatric NAFLD; the closed association of disease development with the cross-talk between different cells and organs; limitations of diagnostic tools borrowed from adult studies and the need of further clinical trial.

Objectives: Nonalcoholic fatty liver disease (NAFLD) in adolescents and children is rapidly becoming one of the most common causes of chronic liver disease worldwide. NAFLD varies from simple fatty liver to nonalcoholic steatohepatitis (NASH) with possible fibrosis. Several studies suggest that oxidative stress plays a central role in several metabolic abnormalities and cellular damage that characterize NAFLD. We investigated whether transition metals and their related proteins were related to NAFLD symptoms and their underlying processes., Methods: We measured copper, iron, ceruloplasmin (Cp) concentration and activity, transferrin (Tf), ferroxidase activity, and ferritin, and we calculated Tf saturation and Cp to Tf ratio (Cp/Tf) as an index of the activity of the antioxidant Cp-Tf system in 100 children with biopsy-proven NAFLD. Pediatric patients were grouped by nonalcoholic fatty liver disease score (NAS) ≥ 5 (30 subjects) and NAS < 5 (70)., Results: Cp distinguished children with NAS ≥ 5 from those with NAS < 5 with an accuracy of 82%. Specifically, a receiver operator characteristics curve showed that a cutoff of 28.6 mg/dL separated NAS ≥ 5 from NAS < 5 with a specificity of 92% and a sensitivity of 76%. The Cp/Tf ratio, as well as copper concentration and Cp activity, decreased in the NAS ≥ 5 group, pointing out an imbalance in metal regulation. Either copper or Cp concentrations were lower in subjects having ballooning., Conclusions: Serum antioxidant capacity owing to Cp failure is strongly associated with NAFLD-related damage. Further studies are, however, required to clarify the role of Cp in NAFLD pathogenesis and to evaluate its potential application as diagnostic marker.

With gradual fall in autopsy all over the world in recent years, the present study aimed to assess the accuracy of clinical diagnosis and efficacy of needle autopsy from the emergency department. Fifty deceased patients, who died in the emergency department during a period of 1 year, were subjected to needle autopsy of the major viscera, using spring-loaded automated biopsy gun, and the findings were correlated with clinical diagnosis. The deceased patients were in the age range of 12 to 80 years (mean [SD], 50.48 [18.41] years). The tissues yielded from various organs were as follows: lungs, 90%; liver, 82%; kidney, 48%; heart, 28%; spleen, 22%; and pancreas, 18%. Before death, 86 clinical diagnoses were recorded, of which 21 (24%) (eg, metabolic encephalopathy, cardiac arrhythmia, diabetic ketoacidosis) were impossible to verify on needle autopsy. A total of 48 new diagnoses, missed by physicians, were revealed by needle autopsy. The most frequently missed diagnoses were liver fatty change (19 patients) and pneumonitis (11 patients). Other frequently missed diagnoses were chronic hepatitis (3 patients) and cancer (2 patients: 1 lung squamous cell carcinoma and 1 lung adenocarcinoma). Major diagnostic errors (Goldman classes I and II) were noted in 16 (32%) of 50 cases. Needle autopsy can be a better alternative in the absence of conventional autopsy.

Objective: The objective of this research was to study the characteristics of fatty liver (FL) in acute pancreatitis (AP) in 2-dimensional in-phase (IP)/out-of-phase (OP) magnetic resonance imaging (MRI)., Methods: Fifty patients with AP (23 men, 27 women; mean age, 44 [SD, 12] years [range, 16-73 years]) were included in this retrospective study. Patients' informed consent was waived. All of them performed abdominal MRI within 72 hours of symptom onset and MRI follow-up. The severity of the AP was graded according to the magnetic resonance severity index (MRSI). The MRSI cutoff was 7.0 points between the mild and the severe AP. Fatty liver in MRI was determined by the hepatic signal intensity difference between OP and IP images. Correlations between the severity of FL and MRSI or serum triglyceride levels were analyzed., Results: Of the 50 patients with AP, FL was found in 66% of patients' MRIs. A close correlation can be seen between the difference of liver signal intensities on IP/OP images and the MRSI (r = 0.83, P < 0.001). Close correlations were found between FL appearance on MRI and serum triglyceride levels in both mild (r = 0.93, P < 0.001) and severe AP (r = 0.95, P < 0.001). During follow-up MRI, the appearance of FL decreased following the decrease in MRSI scores and serum triglyceride levels in both mild and severe AP., Conclusions: Fatty liver in AP is frequently observed in MRI. The appearance of FL in MRI may decrease after subsidence of AP.

Objective: The aims of this study were to assess the confounding effects of hepatic iron deposition, inflammation, and fibrosis on hepatic steatosis (HS) evaluation by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) and to assess the accuracies of MRI and MRS for HS evaluation, using histology as the reference standard., Materials and Methods: In this institutional review board-approved prospective study, 56 patients gave informed consents and underwent chemical-shift MRI and MRS of the liver on a 1.5-T magnetic resonance scanner. To estimate MRI fat fraction (FF), 4 analysis methods were used (dual-echo, triple-echo, multiecho, and multi-interference), and MRS FF was calculated with T2 correction. Degrees of HS, iron deposition, inflammation, and fibrosis were analyzed in liver resection (n = 37) and biopsy (n = 19) specimens. The confounding effects of histology on fat quantification were assessed by multiple linear regression analysis. Using the histologic degree of HS as the reference standard, the accuracies of each method in estimating HS and diagnosing an HS of 5% or greater were determined by linear regression and receiver operating characteristic analyses., Results: Iron deposition significantly confounded estimations of FF by the dual-echo (P < 0.001) and triple-echo (P = 0.033) methods, whereas no histologic feature confounded the multiecho and multi-interference methods or MRS. The MRS (r = 0.95) showed the strongest correlation with histologic degree of HS, followed by the multiecho (r = 0.92), multi-interference (r = 0.91), triple-echo (r = 0.90), and dual-echo (r = 0.85) methods. For diagnosing HS, the areas under the curve tended to be higher for MRS (0.96) and the multiecho (0.95), multi-interference (0.95), and triple-echo (0.95) methods than for the dual-echo method (0.88) (P ≥ 0.13)., Conclusion: The multiecho and multi-interference MRI methods and MRS can accurately quantify hepatic fat, with coexisting histologic abnormalities having no confounding effects.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adolescents in the United States, and most probably also in the rest of the industrialized world.As the prevalence of NAFLD in childhood increases with the worldwide obesity epidemic, there is an urgent need for diagnostic standards that can be commonly used by pediatricians and hepatologists. To this end, we performed a PubMed search of the adult and pediatric literature on NAFLD diagnosis through May 2011 using Topics and/or relevant Authors as search words. According to the present literature, NAFLD is suspected based on the association of fatty liver combined with risk factors (mainly obesity), after the exclusion of other causes of liver disease. The reference but imperfect standard for confirming NAFLD is liver histology. The following surrogate markers are presently used to estimate degree of steatosis and liver fibrosis and risk of progression to end-stage liver disease: imaging by ultrasonography or magnetic resonance imaging, liver function tests, and serum markers of liver fibrosis.NAFLD should be suspected in all of the overweight or obese children and adolescents older than 3 years with increased waist circumference especially if there is a NAFLD history in relatives. The typical presentation, however, is in children ages 10 years and older. The first diagnostic step in these children should be abdominal ultrasound and liver function tests, followed by exclusion of other liver diseases. Overweight/obese children with normal ultrasonographic imaging and normal liver function tests should still be monitored due to the poor sensitivity of these tests at a single assessment.Indications for liver biopsy include the following: to rule out other treatable diseases, in cases of clinically suspected advanced liver disease, before pharmacological/surgical treatment, and as part of a structured intervention protocol or clinical research trial.

Purpose of Review: Steatosis or nonalcoholic fatty liver disease (NAFLD) is commonly associated with abdominal obesity and metabolic disorders. It may evolve to severe liver injuries including nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. HIV-infected patients are aging and face an increased prevalence of abdominal obesity and metabolic disorders. We provide here an overview of NAFLD in HIV-infected patients for a better management of these patients., Recent Findings: Steatosis is observed in 30-40% of HIV-infected patients, associated with increased adiposity and metabolic disorders. Whereas steatosis has probably a benign prognosis, clinically silent lesions of NASH are frequent in patients undergoing liver biopsy with often fibrosis and even cirrhosis. Fibrosis severity is related to age, insulin resistance and stavudine/didanosine-based therapy. Noninvasive markers of fibrosis are useful for the management of NAFLD-suspected patients. In addition to lifestyle changes, new treatment options are emerging and need to be evaluated in these patients. Steatosis is also common in HIV-hepatitis C virus (HCV) co-infected patients and worsens fibrosis progression but does not impact on the rate of sustained virological response., Summary: HIV-infected patients are at risk of NAFLD, a silent disease that can progress to more severe liver injuries. An accurate screening of these patients should be considered to prevent harmful evolution.

Purpose of Review: Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of liver disease in children from the developed world. The purpose of this review is to provide both a focused overview of pediatric NAFLD as well as a summary of the most recent advancements in the field., Recent Findings: Pediatric NAFLD is an underdiagnosed condition which can result in significant liver injury including cirrhosis. Although liver biopsy remains the standard for diagnosis and monitoring disease activity, several noninvasive biomarkers and imaging techniques hold significant promise. Dietary constituents, the intestinal bacterial flora, and sex hormones have been implicated as modulators of disease activity. NAFLD predisposition runs strongly in families and an allele in the PNPLA3 gene has shown a strong association with liver steatosis and hepatic inflammation. Treatment for pediatric NAFLD remains diet and exercise, but vitamin E may be a helpful adjunct., Summary: Pediatric NAFLD shares many features with its adult counterpart but is a distinct entity which requires independent investigation. Our understanding of NAFLD in terms of epidemiology and risk factors has improved considerably but significantly more investigation is required to unravel its pathophysiology and identify novel therapeutic targets.

Background: With the alarming growth in prevalence of paediatric nonalcoholic fatty liver disease (NAFLD), there is a need for noninvasive methods of stratifying disease severity. Our aim was to evaluate a combination of serum biomarkers as a measure of disease activity in paediatric NAFLD., Patients and Methods: Forty-five children with biopsy-proven NAFLD were enrolled. Caspase-cleaved CK18 fragments (CK18 M30), hyaluronic acid, leptin, and adiponectin were measured in serum using enzyme-linked immunosorbent assays and high-sensitivity C-reactive protein using a colorimetric assay., Results: Median age was 12.7 years (55% boys). Median body mass index z score was 1.7. CK18 M30 levels were significantly higher in patients with NAFLD versus controls, median 288 IU/L versus 172 IU/L (P < 0.001), and in those with steatohepatitis, median 347 IU/L versus simple steatosis (NAFLD activity score < 3), median 191 IU/L (P = 0.006). Significant fibrosis (≥F2) could be differentiated from no/minimal fibrosis (

Objectives: The aim of this study was to evaluate the feasibility of 2 established magnetic resonance imaging based techniques to quantify intrahepatic lipids (IHL) within a study population of extremely obese patients by means of a short, wide-bore MR scanner. Fat-selective imaging using a spectral-spatial excitation technique and in-phase/opposed-phase (IN/OP) gradient echo imaging were applied and results were compared. Results for IN/OP technique were corrected for T1- and T2*- relaxation effects. Furthermore, image quality was assessed for both techniques. Differences in regional fat distribution were assessed using parameter maps of voxel-wise calculated IHL., Materials and Methods: MR examinations of 20 extremely obese patients were included in the study (7 males, 13 females; mean age 40.4 +/- 12.6 years; mean body mass index 46.3 +/- 6.6 kg/m2). IHL, in terms of fat signal fractions, was calculated from simultaneously acquired IN/OP-images using a double-echo gradient echo technique. For correction of transverse relaxation effects an additional multiecho gradient echo sequence was applied in each subject, whereas correction of longitudinal relaxation was performed using literature values for T1 of water and lipid protons in the liver parenchyma. A highly selective spectral-spatial excitation technique with 6 binomial radiofrequency pulses was used for fat-selective imaging. In this case, signal intensity of adjacent subcutaneous adipose (approximately 100% fat) was used as an internal reference for IHL quantification., Results: IN/OP-imaging provided sufficient image quality in all subjects, whereas fat-selective imaging was hampered by insufficient homogeneity of the static magnetic field in 1 of 20 subjects. Hepatic T2* values ranged from 20.1 milliseconds to 42.2 milliseconds. Results for IHL from both techniques were highly correlated with r(s) = 0.915 (P < 0.0001). Mean values for IHL were 16.5% +/- 9.2% and 10.6% +/- 7.3%, for IN/OP and spectral-spatial excitation technique, respectively, showing a slightly lower estimation of IHL by the spectral-spatial excitation method. In the examined cohort of extremely obese subjects a relatively high number of 4 out of 20 cases (20%) were found with uneven distribution of IHLs., Conclusions: The presented data confirm that both methods are reliable tools for quantification of IHL, if inherent drawbacks and limitations are taken into account. Inhomogeneity of the static magnetic field observed in examinations of extremely obese patients limits the use of spectral-spatial excitation, if performed without time-consuming shimming procedures. Necessity to correct for transverse and longitudinal relaxation effects using the IN/OP method requires additional measurements and postprocessing procedures, which might hamper the clinical applicability. Moreover, significant regional differences in IHL may exist in some patients especially if pronounced hepatic steatosis is present.

Objectives: To prospectively evaluate a 3-dimensional spoiled gradient-dual-echo (3D SPGR-DE) magnetic resonance imaging (MRI) sequence for the qualitative and quantitative analysis of liver fat content (LFC) in patients with the suspicion of fatty liver disease using histopathology as the standard of reference., Materials and Methods: Thirty-four adult patients (15 women; mean age, 67 +/- 13 years) underwent hepatic 1.5-Tesla 3D SPGR-DE MRI including in-/out-of-phase (IP/OP) and fat-only sequences prior to hepatic surgery with biopsy. Histopathological analyses of total and macrovesicular LFC could be made from biopsies of 39 segments in 23 patients. Two radiologists independently classified steatosis visually using a 4-point scale for IP/OP and fat-only images. Additionally, fat signal fractions (FSF) were calculated from signal intensities on IP/OP (FSF(ip/op)) and fat-only images (FSF(fat-only)). Pearson correlation analysis and Student t test were used to study the relationship between the FSF and LFC as determined by histopathology. The accuracy of MRI in detecting pathologically elevated LFC was assessed by receiver operating characteristic analysis., Results: Histopathology revealed steatosis in 29/39 (74%) segments in 15/23 patients (65%), with a total LFC ranging from <5% to 90%. Inter-reader agreement for visual steatosis grading was moderate (k = 0.53) for IP/OP images and good (k = 0.68) for fat-only images. FSF calculated from IP/OP and fat-only images significantly correlated with LFC from histopathology (both, P < 0.0001). Mean FSF(fat-only) and FSF(ip/op) values significantly differed from total LFC (both, P < 0.0001), whereas mean FSF(fat-only) showed no significant differences to macrovesicular LFC (P = 0.46). Both FSF(fat-only) and FSF(ip/op) performed accurately in discriminating between normal LFC and elevated LFC according to histopathology with good diagnostic accuracy (AUC: 0.85; 95% CI: 0.73-0.89 vs. AUC 0.90, 95% CI: 0.7-1.00)., Conclusions: FSF(fat-only) and FSF(ip/op) derived from 3D SPGR-DE MRI mostly reflect the macrovesicular as opposed to the total LFC from histopathology, whereas both discriminate healthy and fatty liver. Analysis of fat-only images improves interreader-agreement for visual liver steatosis grading.

Purpose of Review: The intent of this review is to provide a concise overview of all recent acquisitions in terms of therapies and early noninvasive diagnostic approaches for nonalcoholic fatty liver disease (NAFLD) in children., Recent Findings: NAFLD is increasingly being diagnosed in children. If undiscovered and if certain risks are present (i.e. obesity), nonalcoholic steatohepatitis, the most severe form of NAFLD, may silently progress to cirrhosis, hepatocarcinoma and liver-related death in adulthood. Current therapies include approaches for reducing the incidence of risk factors (i.e. weight reduction), drugs targeting the major molecular mechanisms thought essential in the pathogenesis of the disease (insulin resistance and oxidative stress) or both, but other novel treatments are under investigation., Summary: Although weight reduction, achieved through a combination of diet and exercise, makes it possible to modify the natural course of simple steatosis, the addition of adequate drugs might also provide a therapeutic action on nonalcoholic steatohepatitis. Moreover, preventive strategies and the design and translation into clinical practice of indices that integrate noninvasive diagnostic tools and serum biomarkers might be a winning approach for improving management of paediatric NAFLD/nonalcoholic steatohepatitis in the coming years.

Background: In liver transplantation, macrovesicular steatosis is a major determinant of graft outcome. Visual assessment of steatosis by the donor surgeon is highly inaccurate, whereas hepatic biopsy is user dependent and cumbersome. Our objective was to validate a novel bioelectrical impedance sensor as a means of objectively quantifying macrovesicular hepatic steatosis and to correlate the results with another surrogate measure of macrosteatosis, hepatic microcirculation., Methods: Fatty (n=36) and lean (n=18) male Zucker rats, 250 to 450 g, were used to achieve varying degrees of steatosis. After a bilateral subcostal incision, hepatic microcirculation was measured using laser Doppler microflowmetry. Low-frequency bioelectrical impedance (LF-BEI) was measured at 1 kHz using a custom-made sensor and instrumentation system. Complete hepatectomy was performed. Hepatic tissue was preserved and stained with hematoxylin-eosin for histology., Results and Conclusion: Both microflow and LF-BEI correlated well with macrosteatosis and each other: Pearson correlation coefficients -0.71, 0.73, and -0.81, respectively. Livers were grouped according to the degree of macrosteatosis: mild (<30%), moderate (30%-60%), and severe (>60%). Both LF-BEI and microflow varied significantly among groups on one-way analysis of variance, although only LF-BEI was capable of discriminating between mild and moderate macrosteatosis on post hoc analysis. Regarding their individual capacities to detect the presence of severe macrosteatosis, both tests were excellent classifiers: receiver operating curve area under the curve 0.885 and 0.9 for LF-BEI and microflow, respectively. However, the bioimpedance apparatus is more rapid and less susceptible to local factors and background noise and could more easily be used in the clinical liver transplantation setting.